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Peer-reviewedCC BY-NC 4.0Technology in Cancer Research & Treatment

Near-Infrared Fluorescent Zwitterionic Folic Acid Probe and Serum CA125 for Enhancing Diagnostic Accuracy of Malignant Ovarian Cancer Ascites

2 more authors
  1. 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
  2. 2Department of Obstetrics and Gynecology, Peking University People’s Hospital, Beijing, China
  3. 3Department of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China

Abstract

Introduction: Accurate detection of malignant cells in ovarian cancer ascites is essential for diagnosis and surgical staging. However, conventional cytological examination is hampered by low sensitivity and interpretive subjectivity. We evaluated a dual-modality strategy combining a near-infrared fluorescent zwitterionic folic acid (ZW-FA) probe targeting folate receptor α with serum biomarkers.

Methods: Ascites and peritoneal lavage specimens were processed into cell blocks. A ZW-FA fluorescence cutoff was exploratorily derived using receiver operating characteristic curve analysis. Diagnostic performance of ZW-FA staining (quantified using ImageJ), hematoxylin-eosin (H&E) staining, serum cancer antigen 125 (CA125), human epididymis protein 4, and the risk of ovarian malignancy algorithm was assessed individually and in combination. Postoperative histopathological diagnosis served as the reference standard.

Results: Among 80 participants, the optimal ZW-FA cutoff was 48.40 (area under the curve = 0.881). Automated fluorescence quantification achieved 100.00% technical reproducibility, providing an objective and consistent readout. ZW-FA correctly classified 2 of 5 (40.00%) specimens that were non-diagnostic by H&E because of insufficient cellularity. In the complete-case comparative analysis of 65 participants, ZW-FA showed higher diagnostic accuracy than H&E staining (86.15% vs. 81.54%). The combination of ZW-FA staining and serum CA125 achieved a sensitivity of 100.00%, a specificity of 81.25%, and an accuracy of 95.38%, exceeding the accuracy of all H&E-based dual-modality strategies (≤ 90.77%).

Conclusion: The ZW-FA/CA125 dual-modality strategy may improve the diagnostic assessment of ovarian cancer ascites and peritoneal lavage specimens, particularly in paucicellular samples. Further validation in larger, independent multicenter cohorts is warranted.

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BibTeX
@article{li2026nearinfrared,
  title = {{Near-Infrared Fluorescent Zwitterionic Folic Acid Probe and Serum CA125 for Enhancing Diagnostic Accuracy of Malignant Ovarian Cancer Ascites}},
  author = {Min Li and Dongxin Liang and Lanbo Zhao and Yiran Wang and Xin He and Wen Zhang and Tiantian Wang and Yadi Bin and Yu Liu and Ruining Ma and Zhe Yang and Siyi Zhang and Yuqi Wang and Qiling Li},
  journal = {Technology in Cancer Research \& Treatment},
  year = {2026},
  month = sep,
  doi = {10.1177/15330338261488986},
  url = {https://doi.org/10.1177/15330338261488986},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Near-Infrared Fluorescent Zwitterionic Folic Acid Probe and Serum CA125 for Enhancing Diagnostic Accuracy of Malignant Ovarian Cancer Ascites
AU  - Min Li
AU  - Dongxin Liang
AU  - Lanbo Zhao
AU  - Yiran Wang
AU  - Xin He
AU  - Wen Zhang
AU  - Tiantian Wang
AU  - Yadi Bin
AU  - Yu Liu
AU  - Ruining Ma
AU  - Zhe Yang
AU  - Siyi Zhang
AU  - Yuqi Wang
AU  - Qiling Li
PY  - 2026
DA  - 2026/09/17
JO  - Technology in Cancer Research & Treatment
DO  - 10.1177/15330338261488986
UR  - https://doi.org/10.1177/15330338261488986
AB  - Introduction: Accurate detection of malignant cells in ovarian cancer ascites is essential for diagnosis and surgical staging. However, conventional cytological examination is hampered by low sensitivity and interpretive subjectivity. We evaluated a dual-modality strategy combining a near-infrared fluorescent zwitterionic folic acid (ZW-FA) probe targeting folate receptor α with serum biomarkers.  Methods: Ascites and peritoneal lavage specimens were processed into cell blocks. A ZW-FA fluorescence cutoff was exploratorily derived using receiver operating characteristic curve analysis. Diagnostic performance of ZW-FA staining (quantified using ImageJ), hematoxylin-eosin (H&E) staining, serum cancer antigen 125 (CA125), human epididymis protein 4, and the risk of ovarian malignancy algorithm was assessed individually and in combination. Postoperative histopathological diagnosis served as the reference standard.  Results: Among 80 participants, the optimal ZW-FA cutoff was 48.40 (area under the curve = 0.881). Automated fluorescence quantification achieved 100.00% technical reproducibility, providing an objective and consistent readout. ZW-FA correctly classified 2 of 5 (40.00%) specimens that were non-diagnostic by H&E because of insufficient cellularity. In the complete-case comparative analysis of 65 participants, ZW-FA showed higher diagnostic accuracy than H&E staining (86.15% vs. 81.54%). The combination of ZW-FA staining and serum CA125 achieved a sensitivity of 100.00%, a specificity of 81.25%, and an accuracy of 95.38%, exceeding the accuracy of all H&E-based dual-modality strategies (≤ 90.77%).  Conclusion: The ZW-FA/CA125 dual-modality strategy may improve the diagnostic assessment of ovarian cancer ascites and peritoneal lavage specimens, particularly in paucicellular samples. Further validation in larger, independent multicenter cohorts is warranted.
SN  - 1533-0346
SN  - 1533-0338
ER  -